Deciphering resistance mechanisms and novel strategies to overcome drug resistance in ovarian cancer: a comprehensive review

Abstract

Ovarian cancer is among the most lethal gynecological cancers, primarily due to the lack of specific symptoms leading to an advanced-stage diagnosis and resistance to chemotherapy. Drug resistance (DR) poses the most significant challenge in treating patients with existing drugs. The Food and Drug Administration (FDA) has recently approved three new therapeutic drugs, including two poly (ADP-ribose) polymerase (PARP) inhibitors (olaparib and niraparib) and one vascular endothelial growth factor (VEGF) inhibitor (bevacizumab) for maintenance therapy. However, resistance to these new drugs has emerged. Therefore, understanding the mechanisms of DR and exploring new approaches to overcome them is crucial for effective management. In this review, we summarize the major molecular mechanisms of DR and discuss novel strategies to combat DR.

Keywords: Chemotherapy; Drug resistance mechanisms; Ovarian cancer; PARP inhibitors; VEGF inhibitor.

Figure 1. Schematic illustration of resistance mechanism of platinum. Resistance to platinum-based drugs has been associated to several mechanisms including influx and efflux transporters, DNA damage repair (DDR), Apoptotic pathways and Autophagy.

Figure 2. Schematic illustration of resistance mechanism of paclitaxel. Resistance to paclitaxel including efflux by P-glycoprotein, Phosphoinositide 3-kinase/protein kinase B pathway, glutathione S transferase 1 and B-cell lymphoma 2 family.

Figure 3. Schematic illustration of resistance mechanism of PARP inhibitor. Resistance to paclitaxel including DNA repair, Efflux transporters and Autophagy.